The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germ-line epsilon RNA promoter.

Kim J, Reeves R, Rothman P, Boothby M
Eur J Immunol. 1995 25 (3): 798-808

PMID: 7705411 · DOI:10.1002/eji.1830250326

The rate of germ-line RNA transcription correlates with the rate of immunoglobulin heavy chain isotype switching. A promoter element for the transcription of RNA from the germ-line mouse immunoglobulin epsilon heavy chain constant region gene is induced by interleukin(IL)-4 and lipopolysaccharide, and is bound at its transcription initiation sites by an IL-4-inducible nuclear protein, NF-BRE. To examine the function of the binding site for this IL-4-inducible complex, substitution mutations were introduced in the promoter. These binding site mutations increased promoter activity and decreased binding of NF-BRE. To investigate the paradox of an IL-4-inducible protein binding to a repressor site in an IL-4-inducible promoter, we determined that the non-histone chromosomal protein HMG-I(Y) binds at the transcription initiation sites of the germ-line epsilon promoter. Assays with antisera against HMG-I(Y) revealed monomeric HMG-I(Y) in nuclear extracts. Cotransfection of an expression construct directing the synthesis of anti-sense HMG-I(Y) RNA also increased promoter activity, consistent with a repressor function of HMG-I(Y). Thus, the data are most consistent with a model in which HMG-I(Y) participates in repression of promoter activity. The effects of IL-4 may include derepression at this site.

MeSH Terms (19)

Animals Base Sequence Cell Line DNA-Binding Proteins Down-Regulation Electrophoresis, Polyacrylamide Gel High Mobility Group Proteins HMGA1a Protein Immunoglobulin E Immunoglobulin Heavy Chains Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data Mutation Promoter Regions, Genetic Recombinant Proteins RNA, Messenger Transfection

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